Circulating hematopoietic stem cells, endothelial progenitor cells and cancer stem cells in hepatocellular carcinoma patients: contribution to diagnosis and prognosis

Abstract

Background and aim: Circulating hematopoietic stem cells (HSCs), circulating endothelial progenitor cells (EPCs) and cancer stem cells (CSCs) contribute to tumor development and progression and can predict patient outcome. The aim of this study was to investigate the frequency of circulating HSCs, EPCs and CSCs in the peripheral blood of patients with hepatocellular carcinoma (HCC) and to explore their potential prognostic significance for HCC patients. Methods: The study included 30 HCC patients and 20 healthy controls. The HSCs and EPCs were enumerated with CD45, CD34, CD133, CD144 markers, while CSCs were enumerated with CD45, CD44, CD133 markers using flow cytometry. Results: The mean percentages of circulating HSCs were significantly lower in HCC patients than the controls (p ¼ .001), whereas the mean percentages of EPCs within the HSCs subpopulation were significantly higher in the HCC patients than the controls (p ¼ .002). The absolute count of CSCs within 100,000 peripheral blood mononuclear cells was 23.5 ± 3.4 in the HCC patients. Also, the mean percentages of circulating HSCs, EPCs and the number of CSCs were significantly increased in patients with multiple hepatic focal lesions than in patients with a single hepatic focal lesion. Both circulating HSCs and EPCs showed significant positive correlation with the level of AFP and with the numbers of CSCs. In the meantime, the numbers of CSCs revealed significant direct correlation with ALT, AST and AFP levels. The one-year overall survival (OS) of the patients was 77.5%. High levels of CSCs, HSCs and EPCs at diagnosis were all associated with worse outcome for the HCC patients. Conclusions: Significant changes in the levels of the circulating HSCs, EPCs and CSCs occur in HCC. These changes help the diagnosis and the prediction of HCC outcome, as higher levels of these cells are associated with worse OS.

High expression of endothelial progenitor cell‑induced angiogenic markers is associated with bile acid levels in HCC

“…Furthermore, the morphology of VEGFR-2-and CD34-positive cells in HCC tumors reported in previous studies were consistent with those in the current study (39)(40)(41). VEGFR-2 and CD34 co-expression has previously been used as a characteristic marker of EPCs (42)(43)(44). Zahran et al (44) reported that EPCs were higher in patients with HCC compared with healthy controls, and increased levels of EPCs were associated with worse OS in HCC.…”

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression

“…Egypt is known to have a high prevalence of HCV infection, and hence the post-hepatitis HCC occurrence is highly expected [28][29][30][31]. This may need intense research, especially in the area of HCC oncogenesis, by exploring the immune-pathogenesis and potential triggers [9,[32][33][34]. Many theories have tried to postulate the potential role of immune cells, especially that of immune-regulatory cells, such as IL-10 + Bregs and Tregs, that have been proven to play a pivotal role in immune down-regulation [35,36].…”

Circulating Tumor-Cell-Associated White Blood Cell Clusters in Peripheral Blood Indicate Poor Prognosis in Patients With Hepatocellular Carcinoma

“…In the past two decades, despite various advances in the treatment of hepatocellular carcinoma (HCC), such as molecular-targeted therapy, radiofrequency ablation, and interventional embolization, surgery remains the most important treatment (3,4). The high metastasis and recurrence rate of HCC indicates that its overall prognosis is still unsatisfactory (5)(6)(7). Metastasis and recurrence are the leading causes of death in patients diagnosed with invasive cancer.…”